It is known that demineralized bone matrix induces new bone formation when implanted in the soft tissue by a process generally designated as matrix induced bone formation (see Urist, M. R., Science, 150: 893-899 (1965)). There have been numerous efforts to extract and identify the active material (or materials) which induces this process, and it has been generally referred to in the literature as bone morphogenetic protein(s) (BMP). It is uncertain whether BMP is a single material or a mixture of materials, and there does not appear to be agreement among the investigators as to which material, if any, is the bone morphogenetic protein. As discussed herein, the term BMP is used to describe the protein having the amino acid sequence shown in FIG. 3 (bovine BMP) or FIG. 5 (human BMP), without the signal peptide.
The therapeutic use of BMP offers considerable advantages over use of traditional bone graft materials. While not intended to be limited by any theory, one hypothesis assumes that BMP initiates the differentiation of tissue cells into osteoblasts (cells that manufacture bone). During a process that replicates normal human fetal development, BMP-induced osteoblasts form cartilage which, over a period of several weeks yields solid bone. Thus BMP may be useful for replacing bone that has been destroyed by disease or accident, for use in treatment of scoliosis victims, for treatment of mal- or mis-formed bone, for use in healing of a fracture, dental reconstruction, hip replacement, bone remodeling, and control of osteoporosis.
It is thus an object of the present invention to produce a functional cartilage and bone growth factor or a component thereof, which is a protein identified by its entire amino acid sequence, which has BMP activity.
It is another object of the present invention to produce this biologically active BMP protein by recombinant DNA technology.